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Authors:
Shanmuganathan, N; Hughes, T. P.Pages: 2125 - 2133Abstract: With the advent of tyrosine kinase inhibitors (TKIs), the goals of therapy in chronic myeloid leukemia (CML) are steadily shifting. Long-term disease control on TKI therapy has been the goal and expectation for most patients. More recently, treatment-free remission (TFR) has entered mainstream practice and is increasingly being adopted as the main goal of therapy. This therapeutic shift not only influences TKI selection but also, has necessitated the refinement and dissemination of highly sensitive and accurate molecular monitoring techniques. Measurement of BCR-ABL1 messenger RNA expression through reverse transcription quantitative polymerase chain reaction, reported according to the International Scale, has become the primary tool for response assessment in CML. Achieving specific time-dependent molecular milestones, as defined by global therapeutic guidelines, has been established as critical in maximizing optimal outcomes while identifying patients at risk of therapy failure. Depth and duration of a deep molecular response have become the new therapeutic targets in patients considered for TFR. Consequently, molecular monitoring in CML has become even more critical to ongoing response assessment, identifying patients with TKI resistance and poor drug adherence, and enabling TFR to be attempted safely and effectively.Keywords: Myeloid Neoplasia, Review ArticlesPubDate: 2018-11-15T09:00:27-08:00DOI: 10.1182/blood-2018-05-848630Issue No:Vol. 132, No. 20 (2018)

Authors:OBrien S. H.Pages: 2134 - 2142Abstract: Heavy menstrual bleeding (HMB) is frequently reported by adolescents. The role of the hematologist is threefold in evaluating such patients: (1) perform a clinical and laboratory evaluation for an underlying bleeding disorder on the basis of the degree of clinical suspicion, (2) identify and manage any concomitant iron deficiency, and (3) provide input to the referring provider regarding the management of HMB, particularly for patients with identified hemostatic defects. Several clues in the menstrual history should raise suspicion for an underlying bleeding disorder, such as menses lasting>7 days, menstrual flow which soaks>5 sanitary products per day or requires product change during the night, passage of large blood clots, or failure to respond to conventional therapies. A detailed personal and family history of other bleeding symptoms should also be obtained. Iron deficiency with and without anemia is commonly found in young women with HMB. Therefore, it is important to obtain measures of hemoglobin and ferritin levels when evaluating these patients. Iron supplementation is often a key component of management in the adolescent with heavy menses and is still needed in those who have received packed red cell transfusions as a result of severe anemia. Strategies for decreasing menstrual blood flow are similar for adults and adolescents with heavy menses, with combined hormonal contraceptives recommended as first-line therapy. However, there are adolescent-specific considerations for many of these agents, and they must be incorporated into shared decision-making when selecting the most appropriate treatment.Keywords: Thrombosis and Hemostasis, Review ArticlesPubDate: 2018-11-15T09:00:27-08:00DOI: 10.1182/blood-2018-05-848739Issue No:Vol. 132, No. 20 (2018)

Authors:
Balatti, V; Tomasello, L, Rassenti, L. Z, Veneziano, D, Nigita, G, Wang, H.-Y, Thorson, J. A, Kipps, T. J, Pekarsky, Y, Croce, C. M.Pages: 2179 - 2182Abstract: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. It is characterized by the accumulation of CD19+/CD5+ lymphocytes and can have variable outcomes. Richter syndrome (RS) is a lethal complication in CLL patients that results in aggressive B-cell lymphomas, and there are no tests to predict its occurrence. Because alterations in microRNA expression can predict the development and progression of several cancers, we investigated whether dysregulation of specific microRNAs can predict RS in CLL patients. Thus, we compared microRNA expression levels in samples from 49 CLL patients who later developed RS with samples from 59 CLL patients who did not. We found that high expression of miR-125a-5p or low expression of miR-34a-5p can predict ~50% of RS with a false positive rate of ~9%. We found that CLL patients predicted to develop RS show either an increase of miR-125a-5p expression (~20-fold) or a decrease of miR-34a-5p expression (~21-fold) compared with CLL patients that are not predicted to develop RS. Thus, miR-125a-5p and miR-34a-5p can be valuable predictor markers of RS and have the potential to provide physicians with information that can indicate the best therapeutic strategy for CLL patients.Keywords: Lymphoid Neoplasia, Brief ReportsPubDate: 2018-11-15T09:00:27-08:00DOI: 10.1182/blood-2018-04-845115Issue No:Vol. 132, No. 20 (2018)